Continuous open-cell polymeric foams containing living cells

• US 5,677,355 A
• Filed: 06/07/1995
• Issued: 10/14/1997
• Est. Priority Date: 08/13/1993
• Status: Expired due to Term

• Current Assignee: Poly-Med, Inc.
• Original Assignee: Smith & Nephew Incorporated (Smith & Nephew PLC)
• Inventors: Roweton, Susan L., Shalaby, Shalaby W.
• Primary Examiner(s): COONEY, JOHN M
• Application Number:
  US08/475,218
• Time in Patent Office: 860 Days
• Field of Search: 521/61, 521/63, 521/84.1, 521/102, 521/149, 521/182, 521/189, 264/41, 264/49, 424/93.1, 424/486
• US Class Current: 521/61
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/38 containing added animal cells organs or tissue containing native cells A61L27/36
• CPC Class Codes: A61L 27/3839 characterised by the site of application in the body materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60
• CPC Class Codes: A61L 27/3847 Bones
• CPC Class Codes: A61L 27/3852 Cartilage, e.g. meniscus
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/56 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: B01D 2323/21 Fillers
• CPC Class Codes: B01D 2325/48 Antimicrobial properties
• CPC Class Codes: B01D 67/003 by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 69/1411 containing dispersed material in a continuous matrix
• CPC Class Codes: B29C 67/202 comprising elimination of a solid or a liquid ingredient
• CPC Class Codes: C08J 2201/042 Elimination of an organic solid phase
• CPC Class Codes: C08J 2205/05 Open cells, i.e. more than 50% of the pores are open
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C08L 23/00 Compositions of homopolymers or copolymers of unsaturated aliphatic hydrocarbons having only one carbon-to-carbon double bond; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C08L 71/12 : Polyphenylene oxides
• CPC Class Codes: C08L 77/00 : Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain of polyhydrazides C08L79/06; of polyamideimides or polyamide acids C08L79/08; Compositions of derivatives of such polymers
• CPC Class Codes: Y10T 428/249958 : Void-containing component is synthetic resin or natural rubbers
• CPC Class Codes: Y10T 428/31504 : Composite [nonstructural laminate]
• CPC Class Codes: Y10T 428/31725 : Of polyamide
• CPC Class Codes: Y10T 428/31931 : Polyene monomer-containing
• CPC Class Codes: Y10T 428/31938 : Polymer of monoethylenically unsaturated hydrocarbon

Abstract

A polymeric foam with continuous, open-cell pores containing living cells suitable for medical applications and methods for preparing these foams. The microporous foams are of controlled pore size that may be utilized in a variety of applications. In general, the foams are characterized in that the pores are continuous and open-celled. In preparing the foams, an organic polymer is melted and combined with a selected solid crystalline fugitive compound, that melts above about 25° C. and/or that sublimates at above about 25° C. or can be extracted, to produce a substantially isotropic solution. The solution is cooled under controlled conditions to produce a foam precursor containing the solidified fugitive composition dispersed through a matrix of the organic polymer. Crystals of fugitive composition are then removed by solvent extraction and/or sublimation, or a like process to produce microcellular foams having a continuous, open-cell structure. After removing the fugitive composition, living cells capable of producing biologically active products are added to the pores to produce a foam containing living cells.

Claims

1. A foam comprising:

an organic polymeric matrix with continuous, open-cell pores dispersed therein; and

living cells producing at least one product, the living cells contained in the pores,

the foams produced by a process comprising the steps of;

combining an organic polymer with a fugitive composition that is a solid cristalline material that melts above 25°

C.

co-melting and co-dissolving the fugitive composition with the polymer to produce a substantially isotropic solution;

solidifying the isotropic solution to produce a foam precursor containing crystals of the fugitive composition;

removing the crystals of the fugitive composition from the foam precursor to produce a continuous, open-cell foam; and

adding selected living cells to the foam for inhabiting the pores and producing at least one product.

2. The foam of claim 1, wherein the foam is of a predetermined shape suitable for implantation into a living skeleton for repairing a wound and the at least one product includes a bone morphogenic protein.

3. The foam of claim 1, wherein the foam is adapted for implantation into a living body and the cells produce at least one biologically active compound that promotes reconstruction of damaged body tissue.

4. The foam of claim 1, wherein the cells utilize a nutrient medium to produce the product.

5. The foam of claim 4, wherein the foam is in the form of hollow fibers.

6. The foam of claim 2, wherein the organic polymer is a bioabsorbable polymer.

7. The foam of claim 3, wherein the organic polymer is a bioabsorbable polymer.

8. The foam of claim 6, wherein the bioabsorbable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polyalkylene oxalates, poly-p-dioxane, polyanhydrides, polymorpholinediones, polycaprolactone, and copolymers thereof.

9. The foam of claim 7, wherein the bioabsorbable polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polyalkylene oxalates, poly-p-dioxane, polyanhydrides, polymorpholinediones, polycaprolactone, and copolymers thereof.

10. The foam of claim 2, wherein the foam is shaped as a prosthetic implant.

11. The foam of claim 3, wherein the foam is shaped as a prosthetic implant.

12. The foam of claim 1, wherein the pore diameter is in the range of about 1 micron to about 400 microns.

13. The foam of claim 1, wherein the living cells are adhered to walls of the pores.